Anti-SAA1 monoclonal antibody, clone SAA1

Abundantly expressed serum amyloid A (SAA) protein under chronic inflammatory conditions gives rise to insoluble aggregates of SAA derivatives in multiple organs resulting in reactive amyloid A (AA) amyloidosis, a consequence of rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, familial Mediterranean fever, and Castleman's disease. An inflammation-responsive transcription factor, SAF (for SAA activating factor), has been implicated in the sustained expression of amyloidogenic SAA under chronic inflammatory conditions. However, its role in the pathogenesis of AA amyloidosis has thus far remained obscure. In this paper we have shown that SAF-1, a major member of the SAF family, is abundantly present in human AA amyloidosis patients. To assess whether SAF-1 is directly linked to the pathogenesis of AA amyloidosis, we have developed a SAF-1 transgenic mouse model. SAF-1-overexpressing mice spontaneously developed AA amyloidosis at the age of 14 mo or older. Immunohistochemical analysis confirmed the nature of the amyloid deposits as an AA type derived from amyloidogenic SAA1. Furthermore, SAF-1 transgenic mice rapidly developed severe AA amyloidosis in response to azocasein injection, indicating increased susceptibility to inflammation. Also, during inflammation SAF-1 transgenic mice exhibited a prolonged acute phase response, leading to an extended period of SAA synthesis. Together, these results provide direct evidence that SAF-1 plays a key role in the development of AA amyloidosis, a consequence of chronic inflammation.

Alzheimer's disease (AD) is a neurodegenerative disorder, characterized by cognitive impairment, progressive neurodegeneration, and amyloid-beta (A beta) lesion. In the neuronal death and disease progression, inflammation is known to play an important role. Our previous study on acute-phase protein serum amyloid A1 (SAA1) overexpressed mice showed that the liver-derived SAA1 accumulated in the brain by crossing the brain blood barrier (BBB) and trigger the depressive-like behavior on mouse. Since SAA1 involved in immune responses in other diseases, we focused on the possibility that SAA1 may exacerbate the neuronal inflammation related to Alzheimer's disease. A APP/SAA overexpressed double transgenic mouse was generated using amyloid precursor protein overexpressed (APP)-c105 mice and SAA1 overexpressed mice to examine the function of SAA1 in A beta abundant condition. Comparisons between APP and APP/SAA1 transgenic mice showed that SAA1 exacerbated amyloid aggregation and glial activation; which lead to the memory decline. Behavior tests also supported this result. Overall, overexpression of SAA1 intensified the neuronal inflammation in amyloid abundant condition and causes the greater memory decline compared to APP mice, which only expresses A beta 1-42.